KR101151690B1 - Method and composition for screening subject for obesity treatment - Google Patents

Abstract

PURPOSE: A method for selecting a subject to be treated with obesity therapy is provided to accurately select the subject among a candidate group with various genetic and environmental differences. CONSTITUTION: A method for selecting a subject to be treated with obesity therapy using a therapeutic agent for obesity comprises: a step of measuring the amount of hypoxanthine in a biological sample; and a step of comparing hypoxanthine amount with the amount of a control group. The biological sample is blood, serum, plasma, lymph, urine, feces, semen, or amniotic fluid. A composition for selecting the subject for the therapeutic agent for obesity contains hypoxanthine binder or enzyme.

Description

Method and Composition for Screening Subject for Obesity Treatment

The present invention relates to methods and compositions for screening subjects for obesity.

More specifically, the present invention relates to a method and composition for selecting a subject that can be treated for obesity by measuring the amount of hypoxanthine in the biological sample of the candidate.

The world's obese population is on the rise and obesity is considered a serious problem in socio-economic terms because it can cause hypertension, diabetes, osteoarthritis, stroke and cancer [1,2].

Previous studies have shown that obesity has a significant effect on lipoprotein metabolism, leading to elevated levels of low-density lipoprotein (LDL) and total cholesterol (TC) [3].

Hyperlipidemia with elevated levels of LDL and TC in the blood is caused by an increase in serum lipoproteins due to primary (primary) hyperlipidemia and other diseases caused by primary defects in the synthesis or degradation of LDL and TC, depending on the cause. It is also classified as secondary (secondary) hyperlipidemia. Primary hyperlipidemia includes familial hypercholesterolemia, familial complex lipoproteinemia, familial hypertriglyceridemia, and secondary hyperlipidemia includes hypothyroidism, diabetes mellitus, renal failure, and obstruction of hepatobiliary obstruction. , Lupus erythematosus (SLE), alcohol (alcohol), steroids (steroids), birth control and birth control pills, obesity, etc.

HMG-Co A reductase, an enzyme that converts HMG-CoA (3-hydroxy-methyl glutaryl coenzyme A) to mevalonate during cholesterol biosynthesis, is a rate-limiting enzyme of cholesterol synthesis and HMG-CoA reductase in liver Degradation of other enzymes is known to increase the activity of the hepatic LDL-receptor to reduce blood cholesterol levels and is widely used in the treatment of related diseases.

Serum cholesterol lowering agents include bile acid-binding resins, cholesterol synthesis inhibitors, nicotinic acid derivatives, and probucol. Among these, simvastatin or lovastatin, a cholesterol inhibitor, inhibits HMG-CoA reductase and induces LDL receptor mRNA expression in the blood. It is known to have an effect of lowering cholesterol.

In addition to these cholesterol synthesis inhibitors in recent years, the illumination for natural substances excellent in cholesterol lowering function while being suitable for long-term use has been made.

Fermented red pepper paste (FRPP), CODEX Standard No. 294R-2009, is one of the most well-known Korean traditional foods, made from rice, meju, salt and red pepper powder and fermented for several months. The unique aroma, taste and color of kochujang are due to the action of microorganisms such as bacteria, yeast and mold during fermentation [5, 6].

There have been several animal models and cell culture studies regarding the anti-obesity effect of kochujang. There has been a document [7] which reported a decrease in fat cell and serum fat levels after kochujang administration, and a report that showed that kochujang increases energy consumption and decreases body fat accumulation [8]. Another study found that the administration of kochujang to 3T3-L1 adipocytes reduced fat accumulation by adipocyte differentiation and lipogenesis [9]. However, these studies focused on analyzing animal and cellular data other than humans.

Humans have various metabolic regulatory systems due to genetic and environmental differences. Thus, the effects of nutritional interventions may be specific to individuals [10]. Blood lipid levels vary according to environmental factors such as race, sex, age, regional climatic conditions, and foods.These are known to treat obesity because they are known to regulate blood lipid levels due to various genetic and environmental factors. The biochemical efficacy of various anti-obesity agents based on natural products is not known yet, so it is more difficult to predict which one will work for you.

Metabolic approaches have been used to elucidate the biochemical efficacy of various natural products, including toxicity screening, drug metabolism, and foods [1113]. Considering that more than 80% of cholesterol is synthesized in the liver and the amount of absorption from food is relatively large and the effect of LDL and cholesterol receptors is inevitably large, the function of the anti-obesity agent is to inhibit the biosynthesis activity of cholesterol and cholesterol Absorption inhibition may be an important determinant. In obesity, an increase in LDL and TC levels in blood is known to be caused by abnormal metabolism. Therefore, metabolic studies related to elevated blood LDL and TC levels in obesity are of paramount importance.

In these studies, urine has been found to be a useful sample of metabolic studies [14]. Kim et al categorized rats into four groups: the normal low calorie group, the normal high calorie group, the high-fat low calorie group and the high-fat high calorie group [15] and examined the differences between metabolites in the urine [15]. Characterization of the urine metabolic profile in the early stages of hypertension with young rats of developing hypertension [16], and William et al. Used magnetic resonance and male obesity using ¹ H-nuclear magnetic resonance (NMR) -based metabolic techniques. Rat metabolic fingerprints were determined [17]. In addition, there are many successful applications of metabolism in combination with multi-variable statistical assays in metabolic fingerprint studies of other biological fluids (such as serum) and tissues [18, 19].

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of cited papers and patent documents are incorporated herein by reference in their entirety, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly explained.

The present inventors have made extensive efforts to discover biomarkers capable of predicting the efficacy of blood lipid control activity in human subjects of obesity treatments. As a result, it was found that hypoxanthin could be used as a biomarker for screening obesity treatment subjects. The present invention has been completed.

Accordingly, it is an object of the present invention to provide a method for selecting a subject for treatment of obesity.

It is another object of the present invention to provide a composition for selecting a subject to be treated for obesity treatment.

Still other objects and advantages of the present invention will become apparent from the following detailed description, claims and drawings.

According to one aspect of the invention, the invention comprises the steps of (a) measuring the amount of hypoxanthine in the biological sample of the candidate; And (b) comparing the amount of hypoxanthin with the amount of hypoxanthin in a control biological sample, wherein the hypoxanthin amount of the candidate is lower than the hypoxanthin amount of the control group, and the obesity of the obesity treatment agent is determined to be the subject of obesity treatment. Provided are methods for screening subjects. Here, the anti-obesity agent is to treat obesity by reducing the amount of total cholesterol (TC) and low-density lipoprotein (LDL) in the blood.

The present inventors have made extensive efforts to discover biomarkers capable of predicting the efficacy of blood lipid control activity in human subjects of obesity treatments. As a result, it was found that hypoxanthin could be used as a biomarker for screening obesity treatment subjects. The present invention has been completed.

Hypoxanthine used in the present invention is a naturally occurring purine derivative whose IUPAC name is 1H-purin-6 (9H) -one (1H-purin-6 (9H) -one). Hypoxanthin is a substance that frequently occurs during purine degradation and is formed from xanthine by the action of xanthine oxidoreductase, and may also be caused by spontaneous deamination of adenine.

The biological sample of the candidate used in the present invention is a sample capable of measuring the amount of hypoxanthin in vivo, and may be, for example, blood, plasma, serum, lymph, saliva, urine, feces, ocular fluid, semen, ascites or amniotic fluid, Preferably, a candidate's urine sample can be used.

The hypoxanthine amount is measured by voltammetry, HPLC (High-performance liquid chromatography), enzyme chromatography, ¹ H-nuclear magnetic resonance ( ¹ H-NMR) analysis, orthogonal projections to latent structures-discriminant analysis The method of measuring hypoxanthin amount is described in detail in the literature (WO2008 / 056990, METHOD AND DEVICE FOR DETERMINING HYPOXANTHINE IN BIOLOGICAL SAMPLES; and WO2007 / 091033, PORTABLE KIT AND METHOD FOR THE ESTIMATION OF TIME). OF DEATH OF A CORPSE BY DETERMINING THE HYPOXANTHINE CONCENTRATION IN THAT CORPSE DEPENDENT ON TEMPERATURE AND TIME.

The control biological sample used in the present invention is the same as the biological sample of the candidate to be used as the biological sample of the person confirmed that there is no change in the amount of TC and LDL in the blood before and after administration of the anti-obesity agent. In other words, when a candidate's urine sample is used, the urine sample is also used as a control biological sample.

The anti-obesity agent used in the present invention can be used without limitation as long as it treats obesity by reducing the amount of total cholesterol (TC) and low-density lipoprotein (LDL) in the blood. Simvastatin, lovastatin, CB (cannabinoid) -I receptor antagonists, phospholipid diesterase-10 inhibitors, orexin (orexin), which inhibit HMG-CoA reductase and induce LDL receptor mRNA expression -1 antagonists, lipase inhibitors and fat absorption receptor inhibitors may be used, but are not necessarily limited thereto.

The anti-obesity agent as a natural substance including foods can be used without limitation as long as it is known in the art to control the amount of TC and LDL in the blood, for example, Kidachiaroe, Aloe vera, Coevisgussa, Ebigususa, Almond ( almond, laurel, anise, saffraan, ginger, cumin, red pepper, miso, ssamjang, cheonggukjang or red pepper paste may be used. In the case of a natural substance obesity treatment containing foods such as kochujang, if it is described in terms of food, it may be expressed as an obesity improving agent. A description of the natural product obesity treatment agent or obesity improving agent having the effect of regulating the amount of TC and LDL in the blood is described in detail in Japanese Patent Laid-Open No. 2003-206225.

In a preferred embodiment of the present invention, the anti-obesity agent is red pepper, miso, ssamjang, cheonggukjang or red pepper paste, most preferably pepper paste.

According to another aspect of the present invention, the present invention is a composition for selecting a subject for the treatment of obesity for the treatment of obesity comprising a binder for hypoxanthine or an enzyme using hypoxanthine as a substrate, wherein Provides a composition characterized in that to treat obesity by reducing the amount of total cholesterol (TC) and low-density lipoprotein (LDL) in the blood.

The composition for screening the obesity treatment subject of the present invention is to facilitate the screening of the above-described obesity treatment subject, and the content in common with the above description is to avoid excessive complexity of the present specification, Omit the description.

 In one embodiment of the invention, the binding agent for hypoxanthine is characterized in that the antibody or aptamer.

The enzyme used in the composition of the present invention can be used without limitation as long as it is an enzyme using hypoxanthine as a substrate. Oxidation-reducing enzymes, transferases, hydrolases, lyases, isomerases and ligases Include. In one embodiment, the enzyme using hypoxanthine as a substrate is xanthine oxidase, xanthine oxidoreductase, hypoxanthine-guanine phosphoribosyl transferase and xanthine dehydro. At least one selected from the group consisting of xanthine dehydrogenase.

The features and advantages of the present invention are summarized as follows:

(Iii) The present invention relates to a method for selecting a subject for treatment of obesity and a composition for selecting a subject for treatment of obesity for an obesity treatment agent.

(ii) The present invention can use hypoxanthine as a biomarker to accurately select subjects for obesity treatment from a candidate group for treatment with various genetic and environmental differences.

Figure 1 shows the ¹ H-NMR spectrum for urine samples before kochujang treatment.
2A shows OPLS-DA-derived score plots of pre-treatment samples (before treatment of TC / LDL-unchanged group; before treatment of TC / LDL-reducing group).
FIG. 2B shows OPLS-DA-derived score plots (1, leucine; 2, isoleucine; 3, valine; 4, methylsuccinate for samples before treatment of TC / LDL-unchanged and TC / LDL-reduced groups 5, 2-methylglutarate; 6, lactate; 7, alanine; 8, acetate; 9, citrate; 10, creatine; 11, taurine; 12, malonate; 13, glycine; 14, mannitol; 15 , t-methylhistidine; 16, histidine; 17, hypofurite; 18, hypoxanthine; 19, formate).
3. Relative intensity (normalized to creatine strength) of hypoxanthine in urine samples before treatment of two kochujang treatment groups (TC / LDL-unchanged and TC / LDL-reduced groups). Independent t -tests were performed to estimate statistically significant differences between the two groups. Error bars represent standard deviations (n = 6 or 8). * Significant difference remains at P <0.05; Powder value is 0.79 (obtained by powder analysis).

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not to be construed as limiting the scope of the present invention. It will be self-evident.

Example

Materials and Methods

1. Preparation of Kochujang Sample

Kochujang was prepared according to the following traditional fermentation method prepared by adding meju and adding it to glutinous rice.

Soybeans containing 10.5% moisture, 5.4% ash, 17.9% fat, 38.7% crude protein and 26.2% carbohydrate were used. The soybeans were soaked at 20 ° C. for 9 hours, dried, sterilized at 121 ° C. for 30 minutes, cooled to 30 ° C. and then ground to powder. Rice was immersed for 12 hours, and sterilized and cooled to the same conditions as above. Soy flour and rice prepared as described above is mixed at a ratio of 6: 4, 0.5% (w / w) rice coji and Bacillus subtilis ( Bacillus ) made using Aspergilus sojae subtilis ) culture broth was added and then molded in a box of 18 cm × 10 cm × 3 cm to prepare meju. Meju prepared as above was stored at 35 ° C., 90% relative humidity for 3 days. The fermented meju was dried for 3-4 days and crushed with a flat roller (Daeyeol Industry, Daejeon, Korea) to use Gochujang. Gochujang was prepared by mixing rice 18.0%, meju powder 6.0%, dried barley sprout 4.0%, salt 10.5%, red pepper powder 17.5% and distilled water 44.0% according to the standard protocol of Sunchang Mun Okrae food (Sunchang, Korea). It contained only 8 kg of 100 kg, fermented and aged for 3 months in the intestine manufacturing facilities of Sunchang Munokrae food to prepare red pepper paste.

Kochujang pill was prepared by mixing rice, kochujang powder, meju powder, dried barley sprouts, salt, soy sauce, black-eyed pea flour and cocoa powder in the ratios shown in Table 1 below. Pills for the placebo-administered group were also prepared in the mixing ratios shown in Table 1, and instead of red pepper paste, seasoning flavor, red pepper flavor, meju powder, soy sauce, fat powder, flour, black eye powder, cocoa powder, salt, honey, caramel pigment and red pigment It was to include. All the samples were used by thawing at room temperature after freezing at -70 ℃ until administration to the test subject group.

main ingredient


Ingredient Kochujang Placebo Content (g) Content (g) Red pepper powder
Rice flour
Dry barley
Salt
Meju powder
Soy sauce 11.9
10.9
5.2
5.2
4.7
2.1 -
-
-
1.1
1.4
6.7


Enhancer Black Bean Powder
Cocoa powder
flour
Fat
honey
Chili Incense
Seasoning Flavor
Caramel coloring 7.5
2.5
-
-
-
-
-
- 9.3
1.4
13.1
6.3
1.4
0.3
0.1
0.1 additive Red cow - 1.5 Gross weight - 50.0 41.3 Freeze Dried Weight - 32.0 32.0 Calories (kcal) - 114.0 113.1

2. Subject

Twenty-eight female volunteers (aged 19-60 years) with a BMI index of 23 kg / m ² or more were recruited and randomly divided into two groups, the kochujang pill group and the placebo pill group. The calories of kochujang pills and placebo pills were set at 114 and 113 kcal / g, respectively. After obtaining informed consent from all 28 volunteers, they were given either kochujang pills or placebo pills three times daily for 12 weeks. The protocol was carried out with the approval of the Functional Food Association Review Committee of Chonbuk National University Hospital.

3. Preparation and Cholesterol Analysis of Plasma and Urine Samples

After 12 hours, the blood of the experimenter was collected and requested to Chonbuk National University Hospital to prepare a plasma sample. Plasma LDL and TC concentrations were measured using a Hitachi 7600-110 analyzer (Hitachi High-Technologies Corporation, Tokyo, Japan) according to the Standard Method of Biochemistry Laboratory at Chonbuk National University Hospital. Urine samples for 24 hours were collected at the Chonbuk National University Hospital. 10 ml of the urine sample was placed in a 15 ml conical tube with 1% sodium azide and stored at −70 ° C. until analysis.

4. NMR  analysis

Before treatment (base level) samples were dissolved in a 40 ° C. water bath, vortexed for 5 seconds, and 0.3 ml of each urine sample was transferred to an Eppendorf tube. Then in 100 g of D ₂ O as a buffer KH ₂ PO ₄ Add 1.232 g and adjust the pH to 6 by adding 1 N NaOD (pH measured with pH meter, Model 720P, Istek, South Korea) to 0.1 MD ₂ O (0.05% 3- (trimethyl as D ₂ O internal standard) Silyl) -propionic-2,2,3,3-d4 acid, including sodium salt). 0.2 ml of D ₂ O was added to 0.3 ml of urine sample and vortexed for a few seconds to mix thoroughly. The mixture prepared as above was placed in a 5 mm NMR tube (Norell, Landisville, NJ) using a pipette [20].

Samples were analyzed using an NMR spectrometer (Avance 600 FT-NMR, Bruker, Germany) at 600.13 MHz, absolute 298 K. The noesygpprld pulse sequence was used to suppress the residual moisture signal. A total of 64 transient data were collected from the spectrum of width 10775.9. An imaging recovery time of 3.04 seconds and a relaxation delay of 1 second were used. Prior to the Fourier transform (FT), an exponential line-broadening function of 0.30 Hz was applied to free induction decays (FID).

5. Statistical Analysis

Using Amix software (version 3.7, Bruker Biospin), the spectral region with δ = 0.00 to 10.00 was divided into 0.04-ppm. The residual moisture signal region from δ = 4.60 to 4.90, with the urea region from δ = 5.60 to 6.00, was excluded from the liquid extract [21]. As a pretreatment method, all data were adjusted around the mean with scaling to unit-variance (UV), and orthogonal projections of latent structure-discriminant analysis (OPLS-DA) were performed using SIMCA-P software (version 12.0, Umetrics, Ume, Sweden). ANOVA and independent t-tests were performed using SPSS software (version 17, SPSS Inc., Chicago, USA), and t-test power analysis was performed using Power and Precision software (version 3.2.0, Biostat, NJ, USA). Was carried out. The mean difference, standard deviation, importance level (p = 0.05) and sample size were used for power value calculation.

Experimental Results and Additional Discussion

1. Biochemical Parameters

As shown in Table 2, the body mass index (BMI) values did not show a significant difference between the kochujang and placebo treatment groups compared to before and after the experiment. In other words, gochujang had no effect on body weight. However, cholesterol control efficacy was significantly higher in the kochujang administration group compared to the placebo administration group. TC and LDL levels in the placebo group showed no significant change over the 12 week experimental period. However, the kochujang-administered group showed a significant decrease of more than 10.7% and 15.7% in TC and LDL, respectively, or showed little change during the 12-week experimental period. In other words, kochujang has been shown to exert two different effects on the human population, which did not differ significantly in basal level TC / LDL levels and BMI levels. As a further experiment on this efficacy, ¹ H-NMR-based metabolic techniques were used to investigate the metabolic profile of the urine samples before the experiment in the kochujang treatment group.

Gochujang (n = 14) Placebo (n = 14) TC / LDL Reduction Group
(n = 8) TC / LDL no change group
(n = 6)


Before treatment


After treatment
Before treatment

After treatment
Before treatment
After treatment TC (mg / dL) 197.0 ± 16.8
175.0 ± 14.2 *
10.7% ^a 207.0 ± 32.8
224.2 ± 23.8
202.2 ± 27.2
197.7 ± 25.9
LDL
(mg / dL) 134.3 ± 17.3
112.8 ± 14.7 *
15.7% ^a 134.8 ± 25.3
149.5 ± 24.8
126.3 ± 27.8 122.9 ± 27.8 BMI 26.4 ± 2.4 26.4 ± 2.3 26.3 ± 2.6 26.5 ± 2.2 27.3 ± 3.1 26.4 ± 3.4

Each value represents the mean ± standard deviation (n = 6 or 8).

* Indicates a significant difference in P <0.05 between pre- and post-dose groups, and the power values for the t-test results of TC and LDL in the TC / LDL reduction group were 0.75 and 0.70, respectively.

^a TC and LDL reduction rate (%) = (post-treated TC / LDL- pretreatment TC / LDL) x 100 / (pretreatment TC / LDL)

2. ^One H- NMR  Spectroscopic analysis

1 shows the respective peak values of representative ¹ H-NMR spectra for urine samples prior to kochujang treatment. The following signals are calculated using the Chenomx NMR Suite software (version 5.1, Chenomx, In., Edmonton, Canada) against chemical shifts with standard compounds: Leucine = 0.94 (d, J = 6.78 Hz); Isoleucine = 0.94 (d, J = 6.78 Hz); Valine = 0.98 (d, J = 6.9 Hz) and 1.02 (d, J = 6.24 Hz); Methylsuccinate = 1.06 (d, J = 7.1 Hz); 2-methylglutarate = 1.06 (d, J = 7.1 Hz); Lactate = 1.34 (d, J = 7.3 Hz); Alanine = 1.46 (d, J = 7.9 Hz); Acetate = 1.94 (s); Citrate = 2.54 (d, J = 14.6 Hz) and = 2.74 (d, J = 17.7 Hz); Creatine = 3.02 (s) and = 3.90 (s); Creatinine = 3.06 (s) and = 4.10; Taurine = 3.42 (t, J = 6.0 Hz); Malonate = 3.34 (s); Glycine = 3.54 (s); Mannitol = 3.66 (dd, J ₁ = 6.5 Hz, J ₂ = 6.0 Hz), = 3.74 (m), = 3.78 (d, J = 9.4 Hz), and = 3.86 (dd, J ₁ = 2.8 Hz, J ₂ = 3.4 Hz); t-methylhistidine = 3.86 (s), = 7.34 (s), and = 8.34 (s), histidine = 7.34 (s) and = 8.34 (s); Hipurate = 7.54 (t, J = 7.2 Hz), = 7.62 (t, J = 7.1 Hz), and = 7.82 (d, J = 7.9 Hz); Hypoxanthine = 8.18 (s); And formate = 8.42 (s).

3. Before dosing with kochujang pre - dose A) of samples Orthogonal Part Smallest Win  analysis( OPLS - DA )

Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) is a preprocessing method that provides improved visualization and reading over partial least squares discriminant analysis (PLS-DA). A predictive component represents a change between groups, which can be predicted based on an orthogonal component representing a change in the group [22]. Thus, OPLS-DA is a useful tool that can distinguish compounds by separating between groups of interest.

Differences in metabolism in urine samples before treatment for the group that had no change in TC / LDL at the administration of kochujang (TC / LDL-no change group) and the group showing a decrease in TC / LDL at the time of kochujang administration (TC / LDL-reduced group). OPLS-DA was used to investigate. 2A shows OPLS-DA-derived score plot, showing that groups can be clearly distinguished. This means that the efficacy of kochujang depends on the metabolic state of the individual. To identify compounds that may contribute to separating each sample in the OPLS-DA model, a loading plot assay was performed (FIG. 2B). The position of the loading plot corresponds to the score plot. Therefore, this means that in this study, the peak of the positive loading plot present at the positive position along the X axis of the score plot is dominant in the sample.

At pretreatment conditions, creatine, taurine, malonate, τ-methylhistidine, histidine and hypurate were higher in the TC / LDL-reducing group and located in the negative region of the loading plot. In the TC / LDL-unchanged group, on the other hand, leucine, isoleucine, valine, methyl succinate, 2-methyl glutarate, lactate, alanine, acetate, citrate, glycine, mannitol, hypoxanthine and formate ( formate), which were located in the positive region of the loading plot.

Independent t -tests were performed to demonstrate the importance of the relative difference in strength of the selected compounds between the two groups. Except for hypoxanthine, there was no significant difference between the relative levels of the selected compounds. The relative intensity of hypoxanthine is shown in FIG. 3, where hypoxanthine levels in TC / LDL-unchanged group were much higher than TC / LDL-reduced group. Previous studies have shown that serum levels of hypoxanthine tend to increase under obesity and oxidative stress conditions [23].

The difference in FRPP efficacy between the TC / LDL-unchanged and TC / LDL-reduced groups may be due to lifestyle, diet, constitution and / or genetic factors. At pretreatment conditions, the urine level of hypoxanthine was significantly lower in the TC / LDL-reducing group compared to the TC / LDL-unchanged group. Therefore, the hypothesis of this study was verified that metabolites in urine can be used as a screening indicator of cholesterol control efficacy of kochujang. Further research is needed to determine the correlation between urine hypoxanthine levels before treatment and other environmental or genetic factors in each individual.

We propose that hypoxanthine can be used as a potential biomarker for subject screening to confirm cholesterol-modulating efficacy of kochujang. In other words, the findings of this study indicate that the methodology can be applied to analyze the biological activity of humans from other natural sources and to identify potential biomarkers for the treatment of individuals with various diseases, including obesity.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

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Claims (9)

A method for screening for obesity subjects for obesity treatments comprising the following steps:
(a) measuring the amount of hypoxanthine in the candidate's biological sample; And
(b) comparing the amount of hypoxanthin to the amount of hypoxanthin in a control biological sample, wherein the anti-obesity agent reduces the amount of total cholesterol (TC) and low-density lipoprotein (LDL) in the blood If the hypoxanthin amount of the candidate is lower than the hypoxanthin amount of the control group, obesity treatment of the obesity treatment agent is determined.
The method of claim 1, wherein the control biological sample is a biological sample of a person having no change in the amount of TC and LDL in the blood before and after administration of the anti-obesity agent.
According to claim 1, wherein the anti-obesity agent for treating obesity by reducing the amount of TC and LDL in the blood CB (cannabinoid) -I receptor antagonist, PDE (phospholipid diesterase) -10 inhibitor, orexin (orexin) -1 antagonist, lipase (lipase) inhibitor, fat absorption receptor inhibitor, aloe vera, almond, laurel, anise, saffraan, ginger, red pepper, miso, ssamjang, cheonggukjang and red pepper paste How to.
The method of claim 1, wherein the anti-obesity agent is red pepper paste.
The method of claim 1, wherein the biological sample is blood, plasma, serum, lymph, saliva, urine, feces, ocular fluid, semen, ascites or amniotic fluid.
6. The method of claim 5, wherein said biological sample is urine.
A composition for selecting a subject for treating obesity for an anti-obesity agent comprising a binder for hypoxanthine or an enzyme using hypoxanthine as a substrate, wherein the anti-obesity agent includes total cholesterol (TC) and A composition for treating obesity by reducing the amount of low-density lipoprotein (LDL).
8. The composition of claim 7, wherein the binding agent to hypoxanthine is an antibody or aptamer.
8. The enzyme according to claim 7, wherein the enzymes that use hypoxanthine are xanthine oxidase, xanthine oxidoreductase, hypoxanthine-guanine phosphoribosyl transferase and xanthine dioxidase. At least one selected from the group consisting of xanthine dehydrogenase.

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